The advent of the first direct-acting antiviral agents have ushered in a new paradigm of hepatitis C treatment, but the current standard of care adds a single new drug to pegylated interferon and ribavirin, increasing the already difficult side effects. Patients and clinicians now await anti-HCV combinations without interferon, several of which are currently under study.

Abbott last week announced initial results from an observed analysis of the Phase 2b Aviator study. Full results will be presented at the American Association for the Study of Liver Disease (AASLD) Liver Meeting next month in Boston.

Below is an edited excerpt from a company press release describing the study findings in more detail.

Full results from the study will be presented at the Latebreaker Session of the Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, November 9-13. Abstracts are available at www.aasld.org.

The observed data analysis used in this abstract does not include six patients who had not yet reached post-treatment week 12 or had missing values (data points) at the time of the abstract submission. All virologic failures and safety discontinuations were included in the analysis.

"There is a significant unmet medical need for genotype 1, the most common form of HCV in the U.S. and Europe," said Kris Kowdley, MD, director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "Results from this phase 2b study suggest that sustained virological response can be achieved without interferon in a high proportion of genotype-1 patients, including patients who have not responded to previous treatment. This is exciting news as we continue to study treatment options for patients."

"Based on the promising results we've seen, Abbott has selected a triple direct acting antiviral regimen, with and without ribavirin for phase 3 development," said Scott Brun, MD, divisional vice president, Infectious Disease Development, Abbott. "The ability to show sustained virological response in these patient populations, without the use of interferon, is extremely encouraging."

The objective of this phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100 mg QD), ABT-267 (25mg QD), ABT-333 (400 mg BID), and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12, or 24 weeks.

Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.

The 12-week regimen of three direct acting antivirals plus ribavirin had the highest SVR12 rates among the 8- and 12-week arms. Results from the 12-week treatment groups containing three direct acting antivirals plus ribavirin are summarized in the chart below.

Treatment-naive
(N=79)

Null responders
(N=45)

BL HCV RNA (log10 IU/mL)

6.5±0.6

6.6±0.5

BL IL28B non-CC genotype

72%

96%

SVR4

78/79 (99%)

42/45 (93%)

OD SVR12

76/77 (99%)

38/41 (93%)

PTW12 data missing*

2

4

Breakthrough

0

3

Relapse

1

0

OD SVR12 (GT1a)

52/53 (98%)

24/27 (89%)

OD SVR12 (GT1b)

24/24 (100%)

14/14 (100%)

OD SVR12 (IL28B non-CC)

54/55 (98%)

36/39 (92%)

*Did not follow up (2 treatment-naive patients and 1 null responder) or have not yet reached PTW12 (3 null responders)

Additional data presented in the abstract represent all 8- and 12-week arms (n=448) of this 14-arm study (571 patients enrolled: 438 treatment-naive and 133 prior null responders). SVR12 rates for other 8- and 12-week regimens ranged from 89-92 percent. Complete SVR12 data for 8- and 12-week arms will be presented at the Liver Meeting.

Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events [AEs]. Of five serious AEs (1 percent), 1 (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naive and null responders, respectively.

About Abbott's HCV Development Programs

Abbott's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational. ABT-450 was discovered during the course of a collaboration between Abbott and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors.

ABT-450 is being developed by Abbott for use in combination with Abbott's other investigational medicines for the treatment of HCV. Abbott is well-positioned to explore combinations and co-formulations of these medicines.

About Abbott

Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries. For more information, see www.abbott.com.